title: Lasting inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst--a novel mechanism for secretory blockade in acute pancreatitis?
abstract: Although overwhelming evidence indicates that neutrophil infiltration is an early event in acute pancreatitis, the effect of neutrophil respiratory burst on pancreatic acini has not been investigated. In the present work, effect of fMLP-induced neutrophil respiratory burst on pancreatic acini was examined. It was found that neutrophil respiratory burst blocked calcium oscillations induced by cholecystokinin or by acetylcholine. Such lasting inhibition was dependent on the density of bursting neutrophils and could be overcome by increased agonist concentration. Inhibition of cholecystokinin stimulation was also observed in AR4-2J cells. In sharp contrast, neutrophil respiratory burst had no effect on calcium oscillations induced by phenylephrine (PE), vasopressin, or by ATP in rat hepatocytes. These data together suggest that inhibition of receptor-mediated calcium oscillations in pancreatic acini by neutrophil respiratory burst would lead to secretory blockade, which is a hallmark of acute pancreatitis. The present work has important implications for clinical treatment and management of acute pancreatitis.
authors.affiliation: Institute of Cell Biology, Beijing Normal University, Beijing 100875, China.
authors.forename: Hui Yuan
authors.initials: HY
authors.lastname: Liang
authors.forename: Zhi Min
authors.initials: ZM
authors.lastname: Song
authors.forename: Zong Jie
authors.initials: ZJ
authors.lastname: Cui
mesh_terms: D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000502:physiology; D000208:Acute Disease; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D045744:Cell Line, Tumor; D008297:Male; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D016897:Respiratory Burst / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579165:Chrna7 protein, rat; D011949:Receptors, Cholecystokinin; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000109:Acetylcholine
keywords: Acute pancreatitis; CCK1 receptors; Calcium oscillations; M3 receptors; Neutrophil respiratory burst; Pancreatic acini